Seek colleagues for potential collaboration or exchange of information and resources. New posts will be featured in the "What's New" section of the website, and we'll also send them out in the SRF Newsletter. Please let us know if you have any success through this feature of the website.

The Maryland Brain Collection: A Unique Resource for Neuroscientists and Psychiatrists—Posted 12 September 2011

As part of the University of Maryland School of Medicine, the Maryland Brain Collection (MBC) offers post-mortem human brain tissue from controls and patients diagnosed with schizophrenia, depression and bi-polar diseases. We encourage neuroscientists and psychiatrists to become collaborators in the use of that precious resource.

Our mission is to collect, store, and distribute high-quality brain tissue to local and international scientists dedicated to improved understanding, care and treatments of psychiatric disorders.

Scientists interested in obtaining postmortem tissue from MBC are invited to submit a tissue request to the MBC steering committee using our website.

The Cognitive Neuroscience Treatment Research to Improve Cognition In Schizophrenia (CNTRICS) initiative executive committee, together with the Division of Adult Translational Research and Treatment Development of the NIMH, is requesting help from basic cognitive scientists and cognitive neuroscientists to nominate tasks developed and validated in your field for translation into use in clinical research and drug discovery. A major barrier to bridging advances in neuroscience and modern drug discovery is a lack of data on the measurement properties of the tasks used in cognitive neuroscience. The CNTRICS initiative is designed to overcome such barriers and to facilitate the translation of knowledge and methods derived from basic animal and human cognitive neuroscience into use in clinical research. Thus, we are requesting your help identifying cognitive tasks that have strong validity in the basic cognitive science and cognitive neuroscience literatures as specific measures of the cognitive processes targeted by CNTRICS. Please see our website for a more detailed description of CNTRICS and the products of the first two meetings of this initiative. The CNTRICS website describes the cognitive constructs that we are targeting, and the criteria for task selection and the goals for task translation. To nominate a task, please use the following link (http://www.surveymonkey.com/s.aspx?sm=LxamXm2VZqS0FfcAbTYeKw_3d_3d). For more information, please contact either Deanna Barch or Cameron Carter.

The National Institute of Mental Health (NIMH), in collaboration with a consortium of pharmaceutical companies and academic researchers, is supporting an initiative (MATRICS-CT) to identify functionally meaningful endpoints for trials of cognition-enhancing drugs for schizophrenia. The need for selection of these endpoints emerged during discussions with the U.S. Food and Drug Administration (FDA), which emphasized that approval of drugs for cognitive impairment associated with schizophrenia (CIAS) would require change in a cognitive performance measure and change in an endpoint that had reasonable face validity. Since registration trials are likely to be relatively brief—perhaps 1 to 6 months—a change in actual community status would not be necessary. Rather, measures selected for these trials are likely to be intermediate measures indicating that an individual is capable of performing a task that is associated with functioning.

The purpose of this letter is to request the nomination of instruments that should be considered as functional intermediate endpoints. Nominated instruments will be evaluated according to selection criteria that were agreed on at the recent MATRICS-CT consensus meeting that you may have attended in August 2007. Instruments that best meet the selection criteria will be included in an NIMH validation study that will be carried out during 2008.

Instruments may be nominated by sending an e-mail to mrevett@mail.ucla.edu before October 1, 2007. If possible, please include a primary reference for the instrument you are nominating as well as any supporting articles.

The program targets common cognitive errors and problem solving biases in schizophrenia (e.g., jumping to conclusions, attributional biases, deficits with theory of mind, incorrigibility), which alone or combined may culminate in the establishment of false beliefs to the point of delusions. The sessions pursue the goal of bringing these distortions to the awareness of patients, and to prompt them to critically reflect on, complement, and change their current repertoire of problem solving. Since psychosis is not a sudden and instantaneous event, but is often preceded by a gradual change in the appraisal of one's cognitions and social environment, empowering metacognitive competence may act prophylactically on psychotic breakdown. Leaflets with homework, which are handed to the participants at the end of each session, assist with this process.

The modules are administered within the framework of a group intervention program. The main purpose of the metacognitive training is to change the "cognitive infrastructure" of delusional ideation. Most aspects of the program are self-explanatory, and allow an individual performance style. The MCT also serves as a channel for knowledge translation, presenting the basic findings of the cognitive neuropsychology of schizophrenia in a format accessible by patients.

We can report that there is already preliminary evidence for its efficacy—d = .43 decrease in positive symptoms (PANSS) over a 4-week trial (2 sessions/week) over and above an active control condition (for a review on the MCT see Moritz and Woodward, 2007). Moreover, Philippa Garety, Kerry Ross and colleagues found that a single MCT session using several exercises from modules 2, 5, and 7 led to a significant decline of jumping to conclusions behavior relative to a control group. There was also tentative evidence for a decrease in delusion conviction in some of the MCT but none of the control patients.

If you have any questions on administration, please do not hesitate to contact us.

I have set out to achieve an ambitious goal (a much-needed one) to revolutionize psychiatry by introducing dynamic systems theory and nonlinear complexity science to the definitions and research of mental disorders. Dynamic systems theory for psychiatry will bridge neurological and psychological conceptualizations, laying the groundwork for a scientific psychiatry and thus for a real prospect of curing psychiatric diseases. To achieve these goals, three levels of scientific activity should progress in parallel, interacting among each other:

1. Mathematical modeling: A theory must be formulated mathematically if it is to be applicable and predictive. Neural network modeling can provide the foundation for such endeavors.

2. Clinical conceptualization: There are advantages to substituting brain-related conceptualizations for the DSM terminology.

3. Theory-related research: According to the new brain-related clinical conceptualizations, imaging and other neuroscientific brain research of mental disorders should coincide with theory predictions. Mathematical models should generate exact quantifiable predictions to validate findings from neuroscientific experiments and imaging data.

I am in the process of establishing a forum to enhance collaborations between psychiatric clinicians and researchers in the field of neuronal network modeling. In the future, I plan to turn the forum into a scientific society. In order to do so, the forum needs a critical mass of members (see members already in the forum). I will need help in registration of the society in a western country (England, U.S., Australia, and so on). I would appreciate any comments on the ideas of the forum, and any help in achieving the above goals.

We are looking for innovative partners in the US on schizophrenia research. We have been working on peptides with bioactive properties in urine from schizophrenic patients, but need a larger subject pool. Because neuroleptics induce peptidases, it is important that patients be drug-free.

All we need is 10 ml of the first morning urine frozen. Alternatively, we can use 10 ml first morning urine with its pH measured and citric acid added to 1 mM, to prevent peptide degradation. (After 48 hours at room temperature more than half the peptides are lost.)

It is a long way from brain to urine, but phenylketonuria and Kanavan syndrome were found via urine analysis. We have found a considerable peptide increase in schizophrenia, some of which are opioids and show clear-cut opium-like effects in animal and in in-vitro studies (Hole et al., 1979). The data have been replicated by Drysdale et al. in the UK, Idet et al. in Hungary (1982), and Cade et al. (2000) in the U.S. In addition, Terenius et al. in Sweden found increased opioid activity measured as increased morphine receptor binding, but without definite isolation of the active peptide (Lindström et al., 1986). (Also relevant, but in postpartum psychosis, Lindström et al., 1984.) We have mass spectrometry on some of the opioids, and immune assay and receptor-binding assay of some of these peptides.

If anyone is interested in collaborating with us, more details shall, of course, be made available. I think we will be able to present a comprehensive story that explains the many peculiarities of this disorder. However, we need to pursue this further and this task is too large for our little group.

We are investigating the protein composition of whole saliva (human) in different psychoemotional states. We found that each psychoemotional state is accompanied by a certain picture of protein composition of whole saliva (Grigoriev et al., 2003). In a group with schizophrenia (40 people), we found two main pictures of protein composition of whole saliva: one that correlates with a depressive state of patients and another that relates to specific psychoemotional activity. I invite researchers who have contact with biochemical labs (analytical electrophoresis of proteins in polyacrylamide gel) to participate in studying protein composition of whole saliva in schizophrenia. I think that biological markers (proteins) of schizophrenia will be found in this medium. The method is simple and accessible. Who is ready to participate?

Based upon new research findings and successful therapeutic
benefits in other neuropsychiatric conditions, it appears that improving
methylation via metabolic approaches may be beneficial in schizophrenia. I
would like to collaborate with clinicians who may be interested in
learning more about this novel and very safe approach. There is an
opportunity for groundbreaking work.

Our group is setting up a huge Data Bank including DNA, plasma, serum samples, as well as the detailed clinical data from at least 2,000 patients with schizophrenia in Beijing, China. At the present, about 500 samples and clinical data have been collected. Our initial plan is to do research at of the following aspects: smoking, hallucinations, antipsychotic-induced body weight gain, clozapine-induced agranulocytosis, cognitive deficit, tardive dyskinesia, and abnormal glucose metabolism. Although we have an excellent plan, there is still a lack of funding to support this project. More importantly, we are looking forward to getting the valuable advice and suggestions on how to make the Data Bank more efficient and integrated. If you are really interested in our project, please feel free to contact me. Thank you so much for your consideration.

We believe this will provide a very efficient approach to identifying breakpoints, and consequently, candidate genes with specified disruptions associated with disease. As an eminent colleague opined: "It took 10 YEARS to clone the gene related to the initial cytogenetic anomaly we identified and (given marked advances in genome technology) 10 WEEKS to clone the gene related to the most recent one we've found."

These genes could be further evaluated via linkage, linkage
disequilibrium, and sequencing studies in other populations to examine
their generalizability. We'd like to see the results of these screens
made publicly available as soon as they are vetted to provide a useful
resource for the schizophrenia genetics research community. We're very much looking forward to talking further with interested colleagues.